&lt;p&gt;Anticancer Effects of ACT001 via NF-κB Suppression in Murine Triple-Negative Breast Cancer Cell Line 4T1&lt;/p&gt;

Liu, Yanyang; Wang, Li; Liu, Jiewei; Xie, Xiaoxiao; Hu, Haoyue; Luo, Feng

doi:10.2147/cmar.s244748

Cited by 17 publications

(10 citation statements)

References 25 publications

(26 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, a patient with relapsed and drug‐free GBM maintained complete remission for 40 months after receiving ACT001. By inhibiting phospho‐NF‐κB and IκB‐α in triple‐negative breast cancer cells, ACT001 decreases granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), promotes apoptosis, and reduces angiogenesis 19 . In addition, ACT001 also induces cell cycle arrest, apoptosis, and the generation of reactive oxygen species in hepatocellular carcinoma cells by inhibiting the PI3K/AKT pathway 21 .…”

Section: Introductionmentioning

confidence: 99%

“…By inhibiting phospho‐NF‐κB and IκB‐α in triple‐negative breast cancer cells, ACT001 decreases granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), promotes apoptosis, and reduces angiogenesis. 19 In addition, ACT001 also induces cell cycle arrest, apoptosis, and the generation of reactive oxygen species in hepatocellular carcinoma cells by inhibiting the PI3K/AKT pathway. 21 However, the mechanism of ACT001 is less well understood, especially in NSCLC.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

ACT001 inhibits the proliferation of non‐small cell lung cancer cells by upregulating NKTR expression

2022

View full text Add to dashboard Cite

Background Lung cancer, the primary cause of cancer‐related deaths worldwide, is diagnosed at an advanced stage and has a poor prognosis. Non‐small cell lung cancer (NSCLC) is a major histological type of lung malignancy. This study investigated the effect of ACT001, a novel sesquiterpene lactone derivative, on the proliferation of NSCLC cells and explored the underlying mechanism. Methods The effect of ACT001 on cell proliferation was examined by clone formation and MTT assay. Differentially expressed genes and enrichment pathways were analyzed by RNA‐seq. Flow cytometry and cell cycle‐related protein expression analysis were performed to study the cell cycle. Phosphorylated AKT was detected to explore the mechanism in natural killer cell triggering receptor (NKTR) KD cells with AKT activator and/or inhibitor. The therapeutic effect of ACT001 in vivo was studied in the xenograft tumor model. Results ACT001 inhibited the proliferation and G1/S transition in NSCLC cell lines. By RNA‐seq analysis, NKTR may be the target of ACT001. Moreover, knockdown NKTR promoted cell proliferation and reversed the effects of ACT001. In addition, ACT001 inhibited AKT phosphorylation, but NKTR knockdown promoted AKT phosphorylation. Conclusion Our results suggested NKTR may be the target of ACT001 in NSCLC. ACT001 holds promise as a novel method for the treatment of NSCLC.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

ACT001 inhibits the proliferation of non‐small cell lung cancer cells by upregulating NKTR expression

2022

View full text Add to dashboard Cite

show abstract

“…Similarly, crambescidin 800 (C800), a guanidine alkaloid isolated from sponge, could decrease the phosphorylation of Akt, NF-κB and MAPK, resulting in apoptosis in TNBC cells [ 81 ]. A novel derivative of sesquiterpene lactone, ACT001, was found to suppress tumor angiogenesis and the accumulation of myeloid-derived suppressor cells (MDSCs) of 4T1 tumor-bearing mice, by inhibiting the activity of NF-κB pathway and successively inducing apoptosis [ 82 ]. Cedarone acetate was a compound obtained by acetylation modification of original cedarone molecule; when compared with the original molecule, it could enhance the cytotoxic activity and induce apoptosis through downregulating the level of NF-κB and matrix metallopeptidase 9 (MMP9) [ 83 ].…”

Section: Targeting Apoptotic Pathways With Small-molecule Compounds I...mentioning

confidence: 99%

Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies

et al. 2022

View full text Add to dashboard Cite

Triple-negative breast cancer (TNBC) is a subtype of human breast cancer with one of the worst prognoses, with no targeted therapeutic strategies currently available. Regulated cell death (RCD), also known as programmed cell death (PCD), has been widely reported to have numerous links to the progression and therapy of many types of human cancer. Of note, RCD can be divided into numerous different subroutines, including autophagy-dependent cell death, apoptosis, mitotic catastrophe, necroptosis, ferroptosis, pyroptosis and anoikis. More recently, targeting the subroutines of RCD with small-molecule compounds has been emerging as a promising therapeutic strategy, which has rapidly progressed in the treatment of TNBC. Therefore, in this review, we focus on summarizing the molecular mechanisms of the above-mentioned seven major RCD subroutines related to TNBC and the latest progress of small-molecule compounds targeting different RCD subroutines. Moreover, we further discuss the combined strategies of one drug (e.g., narciclasine) or more drugs (e.g., torin-1 combined with chloroquine) to achieve the therapeutic potential on TNBC by regulating RCD subroutines. More importantly, we demonstrate several small-molecule compounds (e.g., ONC201 and NCT03733119) by targeting the subroutines of RCD in TNBC clinical trials. Taken together, these findings will provide a clue on illuminating more actionable low-hanging-fruit druggable targets and candidate small-molecule drugs for potential RCD-related TNBC therapies. Graphical abstract

show abstract

“…ACT001 ( Figure 6 C) is the fumarate salt of dimethylaminomicheliolide as an orally available derivative of MCL, synthesized from PN by Accendatech Co., Ltd. (Tianjin, China) [ 194 ]. ACT001 has a strong anticancer action in breast cancer cells [ 195 , 196 ]. It has been shown that ACT001 is also able to inhibit the proliferation of glioma stem cells (GSCs) [ 197 ].…”

Section: Pathenolide Therapeutic Potential and Parthenolide Analoguesmentioning

confidence: 99%

Parthenolide and Its Soluble Analogues: Multitasking Compounds with Antitumor Properties

et al. 2022

View full text Add to dashboard Cite

Due to its chemical properties and multiple molecular effects on different tumor cell types, the sesquiterpene lactone parthenolide (PN) can be considered an effective drug with significant potential in cancer therapy. PN has been shown to induce either classic apoptosis or alternative caspase-independent forms of cell death in many tumor models. The therapeutical potential of PN has been increased by chemical design and synthesis of more soluble analogues including dimethylaminoparthenolide (DMAPT). This review focuses on the molecular mechanisms of both PN and analogues action in tumor models, highlighting their effects on gene expression, signal transduction and execution of different types of cell death. Recent findings indicate that these compounds not only inhibit prosurvival transcriptional factors such as NF-kB and STATs but can also determine the activation of specific death pathways, increasing intracellular reactive oxygen species (ROS) production and modifications of Bcl-2 family members. An intriguing property of these compounds is its specific targeting of cancer stem cells. The unusual actions of PN and its analogues make these agents good candidates for molecular targeted cancer therapy.

show abstract

<p>Anticancer Effects of ACT001 via NF-κB Suppression in Murine Triple-Negative Breast Cancer Cell Line 4T1</p>

Cited by 17 publications

References 25 publications

ACT001 inhibits the proliferation of non‐small cell lung cancer cells by upregulating NKTR expression

ACT001 inhibits the proliferation of non‐small cell lung cancer cells by upregulating NKTR expression

Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies

Parthenolide and Its Soluble Analogues: Multitasking Compounds with Antitumor Properties

Contact Info

Product

Resources

About